The DING Family of Phosphate Binding Proteins in Inflammatory Diseases

González, Daniel H.; Elias, Mikael; Chabrière, Éric

doi:10.1007/978-3-319-07320-0_4

Cited by 4 publications

(11 citation statements)

References 35 publications

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“…This is consistent with the sub-angstrom X-ray structure analysis. 18,19,23 In the sub-angstrom X-ray crystallography studies of PfluDING, only one proton on oxygen atoms of the phosphate was observed at pH 4.5 and 8.5. PfluDING and E. coli PBP are topologically similar with a structural rmsd value of 1.34 Å over 228 Cα carbons and 0.23 Å over all heavy atoms in the binding pocket.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…This again agrees with sub-angstrom crystallography studies. 18,19,23 It should be noted that constant-pH MD is an alternative way to determine the protonation state of titratable groups. 43,44 In addition, the binding free energies of 1H phosphate are similar for the wild-type and the mutant protein, consistent with experimental measurements.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…While its effect on protein phosphate binding is not as significant as indicated by gas-phase calculations, 16 – 17 the LBHB is responsible for discriminating arsenate and other similar tetrahedral oxyanions. 9, 18 – 19…”

Section: Introductionmentioning

confidence: 99%

“…While its effect on protein phosphate binding is not as significant as indicated by gas-phase calculations, 16,17 the LBHB is responsible for discriminating arsenate and other similar tetrahedral oxyanions. 9,18,19 Despite numerous studies on PBPs, questions remain about the binding mechanism. It is believed that PBP can bind to either 1H or 2H phosphate based on the observation that Escherichia coli (E. coli) PBP has similar affinities for phosphate at pH 4.5 and 8.5.…”

Section: ■ Introductionmentioning

confidence: 99%

“…9 However, sub-angstrom X-ray crystallography studies of a topologically similar protein PfluDING (Pseudomonas fluorescens PBP) showed that only 1H phosphate was present in the binding pocket at both pH 4.5 and 8.5, suggesting that PBP should follow a similar binding mechanism. 18,19,23 It seems that the conserved experimental affinities and the 1H-specific binding mode in sub-angstrom crystal structures cannot be reconciled with each other.…”

Section: ■ Introductionmentioning

confidence: 99%

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Elucidating the Phosphate Binding Mode of Phosphate-Binding Protein: The Critical Effect of Buffer Solution

Jing

Liu

et al. 2018

J. Phys. Chem. B

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Phosphate is an essential component of cell functions, and the specific transport of phosphorus into a cell is mediated by phosphate-binding protein (PBP). The mechanism of PBP-phosphate recognition remains controversial: on the basis of similar binding affinities at acidic and basic pHs, it is believed that the hydrogen network in the binding site is flexible to adapt to different protonation states of phosphates. However, only hydrogen (1H) phosphate was observed in the sub-angstrom X-ray structures. To address this inconsistency, we performed molecular dynamics simulations using the AMOEBA polarizable force field. Structural and free energy data from simulations suggested that 1H phosphate was the preferred bound form at both pHs. The binding of dihydrogen (2H) phosphate disrupted the hydrogen-bond network in the PBP pocket, and the computed affinity was much weaker than that of 1H phosphate. Furthermore, we showed that the discrepancy in the studies described above is resolved if the interaction between phosphate and the buffer agent is taken into account. The calculated apparent binding affinities are in excellent agreement with experimental measurements. Our results suggest the high specificity of PBP for 1H phosphate and highlight the importance of the buffer solution for the binding of highly charged ligands.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Elucidating the Phosphate Binding Mode of Phosphate-Binding Protein: The Critical Effect of Buffer Solution

Jing

Liu

et al. 2018

J. Phys. Chem. B

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Analysis of Pelagia noctiluca proteome Reveals a Red Fluorescent Protein, a Zinc Metalloproteinase and a Peroxiredoxin

et al. 2017

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Pelagia noctiluca is the most venomous jellyfish in the Mediterranean Sea where it forms dense blooms. Although there is several published research on this species, until now none of the works has been focused on a complete protein profile of the all body constituents of this organism. Here, we have performed a detailed proteomics characterization of the major protein components expressed by P. noctiluca. With that aim, we have considered the study of jellyfish proteins involved in defense, body constituents and metabolism, and furthered explore the significance and potential application of such bioactive molecules. P. noctiluca body proteins were separated by1D SDS-PAGE and 2DE followed by characterization by nanoLC-MS/MS and MALDI-TOF/TOF techniques. Altogether, both methods revealed 68 different proteins, including a Zinc Metalloproteinase, a Red Fluorescent Protein (RFP) and a Peroxiredoxin. These three proteins were identified for the first time in P. noctiluca. Zinc Metalloproteinase was previously reported in the venom of other jellyfish species. Besides the proteins described above, the other 65 proteins found in P. noctiluca body content were identified and associated with its clinical significance. Among all the proteins identified in this work we highlight: Zinc metalloproteinase, which has a ShK toxin domain and therefore should be implicated in the sting toxicity of P. noctiluca.; the RFP which are a very important family of proteins due to its possible application as molecular markers; and last but not least the discovery of a Peroxiredoxin in this organism makes it a new natural resource of antioxidant and anti-UV radiation agents.

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Improving combination antiretroviral therapy by targeting HIV-1 gene transcription

Douce¹,

Ait-Amar²,

Far³

et al. 2016

Expert Opinion on Therapeutic Targets

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Combination Antiretroviral Therapy (cART) has not allowed the cure of HIV. The main obstacle to HIV eradication is the existence of quiescent reservoirs. Several other limitations of cART have been described, such as strict life-long treatment and high costs, restricting it to Western countries, as well as the development of multidrug resistance. Given these limitations and the impetus to find a cure, the development of new treatments is necessary. Areas covered: In this review, we discuss the current status of several efficient molecules able to suppress HIV gene transcription, including NF-kB and Tat inhibitors. We also assess the potential of new proteins belonging to the intriguing DING family, which have been reported to have potential anti-HIV-1 activity by inhibiting HIV gene transcription. Expert opinion: Targeting HIV-1 gene transcription is an alternative approach, which could overcome cART-related issues, such as the emergence of multidrug resistance. Improving cART will rely on the identification and characterization of new actors inhibiting HIV-1 transcription. Combining such efforts with the use of new technologies, the development of new models for preclinical studies, and improvement in drug delivery will considerably reduce drug toxicity and thus increase patient adherence.

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The DING Family of Phosphate Binding Proteins in Inflammatory Diseases

Cited by 4 publications

References 35 publications

Elucidating the Phosphate Binding Mode of Phosphate-Binding Protein: The Critical Effect of Buffer Solution

Elucidating the Phosphate Binding Mode of Phosphate-Binding Protein: The Critical Effect of Buffer Solution

Analysis of Pelagia noctiluca proteome Reveals a Red Fluorescent Protein, a Zinc Metalloproteinase and a Peroxiredoxin

Improving combination antiretroviral therapy by targeting HIV-1 gene transcription

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